Long-range looping of a locus control region drives tissue-specific chromatin packing within a multigene cluster

Nucleic Acids Research
Yu-Cheng TsaiS A Liebhaber

Abstract

The relationships of higher order chromatin organization to mammalian gene expression remain incompletely defined. The human Growth Hormone (hGH) multigene cluster contains five gene paralogs. These genes are selectively activated in either the pituitary or the placenta by distinct components of a remote locus control region (LCR). Prior studies have revealed that appropriate activation of the placental genes is dependent not only on the actions of the LCR, but also on the multigene composition of the cluster itself. Here, we demonstrate that the hGH LCR 'loops' over a distance of 28 kb in primary placental nuclei to make specific contacts with the promoters of the two GH genes in the cluster. This long-range interaction sequesters the GH genes from the three hCS genes which co-assemble into a tightly packed 'hCS chromatin hub'. Elimination of the long-range looping, via specific deletion of the placental LCR components, triggers a dramatic disruption of the hCS chromatin hub. These data reveal a higher-order structural pathway by which long-range looping from an LCR impacts on local chromatin architecture that is linked to tissue-specific gene regulation within a multigene cluster.

References

Jun 1, 1989·The Journal of Clinical Investigation·S A LiebhaberN E Cooke
Jun 25, 1983·Nucleic Acids Research·G S BarshR E Gelinas
Dec 1, 1995·Molecular and Cellular Biology·B K JonesN E Cooke
May 2, 2000·The Journal of Biological Chemistry·F ElefantS A Liebhaber
Jul 19, 2006·Molecular and Cellular Biology·Eung Jae YooStephen A Liebhaber
May 25, 2007·Nature·Adrian Bird
Jul 20, 2007·Molecular and Cellular Biology·Atsushi P KimuraStephen A Liebhaber
Jul 21, 2007·Nature Protocols·Hélène HagègeThierry Forné
Oct 5, 2007·Current Opinion in Genetics & Development·Julie A Wallace, Gary Felsenfeld
Jul 1, 2009·Cell·Jennifer E Phillips, Victor G Corces
Sep 8, 2012·Nature·UNKNOWN ENCODE Project Consortium
Nov 6, 2012·Biochimica Et Biophysica Acta·Judith Marsman, Julia A Horsfield
Feb 23, 2013·Molecular and Cellular Biology·Yugong HoNancy E Cooke
Mar 19, 2013·Cell·Matthias Merkenschlager, Duncan T Odom
Jun 15, 2013·Nucleic Acids Research·Nathan Harmston, Boris Lenhard
Feb 25, 2014·Nucleic Acids Research·Yu-Cheng TsaiStephen A Liebhaber
Mar 13, 2014·Nature Reviews. Genetics·Chin-Tong Ong, Victor G Corces
Sep 15, 2014·Trends in Cell Biology·Elena Gómez-Díaz, Victor G Corces

❮ Previous
Next ❯

Citations

Apr 17, 2018·Endocrinology·Shutan LiaoJo K Perry
Apr 29, 2020·ELife·Steve W Miller, James W Posakony
Jun 27, 2019·The New England Journal of Medicine·Shlomo Melmed
May 16, 2018·American Journal of Physiology. Endocrinology and Metabolism·Yan JinPeter A Cattini
Jul 3, 2021·Genes·Sergey V RazinOlga V Iarovaia

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.